Patients with uncontrolled epilepsy may have impairment of language and memory associated with their seizures. In addition, it is critical to map these functions when surgery is being considered. We are using imaging methods in an effort to replace more invasive approaches to detecting the effects of epilepsy on language and memory, and for preoperative mapping. Methods: We use positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to map language and memory in patients with temporal lobe epilepsy to perform non-invasive evaluation of functional cortex, and study the effect of epilepsy on cognitive anatomy in children and adults with seizures. Our studies in both normal volunteers and patients with uncontrolled seizures have shown that imaging evaluation compares well with more invasive procedures such as electrostimulation mapping and the intra-carotid sodium amytal test. We also evaluate the effect of seizures on the development of functional cognitive anatomy. Our previous studies have demonstrated that different fMRI paradigms may be used as probes of different aspects of language processing and that visual analysis is equivalent to quanitative region of interest analysis. We have examined patients deemed to have atypical language and find that fMRI demonstrates several patterns of atypical language processing that involve a distributed network in the left hemisphere and its right homologues. Activation outside there areas is rare, 80% of atypical language activation involves some form of regional activation. We have also examined the factors associated with language re-organization and find them associated with early age seizure onset, atypical handedness and remote cause. Patients with non-lesional neocortical epilepsy have a 30% incidence of atypical language, mesial temporal sclerosis 23%, tumor and focal dysplasia 14% each. All patients with a history of left hemisphere stroke have some form of language reorganization. fMRI language tasks reliably identify language areas but memory paradigms have been problematic. We examined an auditory description decision task for hippocampal activation and compared to IAT in 25 patients using a hippocampal mask analysis. We found that activation in hippocampus mostly reflected language dominance except where the hippocampus was sclerotic. We found poor correlation with IAT laterality indices, and only fair correlation between dominant HF activation and IAT memory capacity based on IAT. Arterial spin-labeled MRI is a new techniques that allows direct measurement of cerebral blood flow, as oppsoed to the indirect blood oxygenation level technique. this approqch may be less sensitive to perfusion limitations, nad provide more accurate data, particulalry in children. We have bene studying patients and normal volunteers in a comparions of ASL with the established 15-O water PET technique for cerebral blood flow estimation. PET was performed on a GE Signa 3T MRI scanner using a proximal inversion with a control for off resonance effects (PICORE)- quantitative imaging of perfusion using a single subtraction, second version (QUIPSS II) ASL sequence to estimate baseline flow. (TR/TE = 2500ms/30ms, TI1/TI2 = 700ms/1400ms, FOV = 24cm, slice thickness = 7mm, matrix: 64x64, 5 axial slices). Images were corrected for subject motion. Flow values were averaged over 150 time points, in each temporal lobe. For 15O-PET, we used a GE (Waukesha, WI, USA) Advance Tomograph (FWHM = 6-7 mm), scanning 35 simultaneous slices with 4.25 mm slice separation. During scanning, in a quiet, dim room with eyes closed and ears unoccluded, a thermoplastic facemask held the subject s head in place. 10 mCi 15O-H2O was injected, and scanning performed for two minutes, using continuous arterial blood measurements with an automatic blood counter. Quantitative CBF values were obtained in regions drawn on co-registered structural MRI. For comparison with ASL-MRI, regional CBF from hippocampal formation, amygdala, parahippocampal gyrus, and fusiform gyrus were averaged. For both ASL-MRI and 15O-PET, an asymmetry index (AI) was derived using the formula: 2 * (ipsilateral-contralateral)/ (ipsilateral+contralateral).Our data suggest that ASL-MRI using QUIPSS II saturated pulse may be a useful tool for identifying temporal lobe epileptogenic zones, providing CBF data comparable to 15O-PET. Current Studies: After establishing and validation ASL with PET in adults we are embarking on fMRI rest and activation studies using arterial spin tagging at 3T that will examine developmental differences in cerebral blood flow and BOLD signal response. We also plan to study the effects of temporal lobectomy on the functional anatomy of language and working memory. Recent evidence suggests a central role for the anterior pole and the amygdala in these distributed neural systems. We will stuyd the role of anterior temporal lobe structures in modulating memory networks involved in semantic and affective processing. Using fMRI, patients with temporal lobe epilepsy (TLE) will be evaluated before and after anterior temporal lobectomy and behavioral results as well as fMRI activation patterns will be compared to those of age-,sex- and education-matched healthy controls. The study of the effects of a planned surgical lesion on cortical networks in humans has the potential to significantly contribute to the characterization of memory circuitry and can form the basis for the development of novel treatment strategies for patients with social and cognitive dysfunctions.